A solitary crateriform ulcer of the lower lip: a case report with review of literature.

Keratoacanthoma (KA) is a relatively common skin lesion. We report a case of KA-mimicking squamous cell carcinoma in a 40-year old smoker, who was also having speckeled leukoplakia on the buccal mucosa. The present case highlights the importance of histopathological diagnosis, as the treatment in latter case is aggressive, which is unnecessary if attempted with KA. Moreover, the present report provides an overview of such lesions, which could be encountered in clinical situations for which definitive diagnosis is of paramount importance before the starting of treatment plan.

Introduction

Keratoacanthoma (KA) is a distinctive benign tumor that displays rapid growth with clinical and histologic pattern often suggestive of squamous cell carcinoma.[1] It may be considered as “an abortive malignancy which rarely progresses into an invasive squamous cell carcinoma.”[2] The term KA was first used by Rook and Whimster (1950) to describe a common, self-healing epithelioma of the skin occurring mainly on the exposed areas of the elderly people as an infiltrating, self-limited, localized growth of squamous cells.[34] These lesions occur as painless, rapidly growing, raised nodules of size 1-2 cm, exhibiting a centrally depressed, keratin-filled crater descriptively referred to as “volcano.”.[56] The peak incidence of KA is between the ages of 45 and 69 years with a majority of tumors occurring on exposed parts of the skin, lips, cheeks, nose, and dorsum of hands.[257] It is more frequent in light-skinned individuals and affects predominantly males in the ratio of 3:1.[78]

The present report document a case of KA of lip that misled us to a clinical diagnosis of squamous cell carcinoma because of its clinical appearance and concomitant presence of bilateral leukoplakia of the buccal mucosa. Crucial role of histopathology is highlighted in such clinical entities because of drastic difference in their overall management and prognosis.

Case Report

A 50-year male patient reported to the Out Patient Department of Oral Medicine and Radiology of I.T.S. Centre for Dental Studies and Research, Muradnagar, India, with the chief complaint of a painless lip ulceration for the last one and half month. He stated that the lesion that appeared six weeks earlier started as a small hard papule with a central depression, and it grew rapidly for the first 4 weeks and then appeared to have stabilized. There was no description of any previous local trauma. However, patient reported continuous out-door activities in sun to earn his livelihood and history of heavy smoking for the past 20 years. His medical history was otherwise unremarkable.

The patient was moderately built and nourished for his age with all vital signs within normal limits. The local examination revealed a red and gray, raised, well circumscribed, sessile, nodular lesion measuring 2 cm in its greatest dimension with raised edges at the vermilion border of the lower lip on the left side of the face [Figure 1]. The center of the growth was slightly umblicated, erythematous and filled with a yellow cheesy material and the periphery appeared stippled with brown crustations. There was absence of associated regional lymphadenopathy as well as tenderness, bleeding and purulent discharge. Intraoral examination revealed presence of grayish white keratotic patch on both sides of buccal mucosa measuring 1.5 cm × 1.5 cm with an extension from the corner of the mouth to the second premolar region. Surface characteristically revealed corrugated appearance even on stretching the mucosa with absence of bleeding points or associated tenderness on palpation. Based on the clinical appearance and significant tobacco habit a provisional diagnosis of squamous cell carcinoma in an existing leukoplakia was made.

Figure 1

Clinical picture

For confirmation, an excisional biopsy for lip lesion and an incisional biopsy from left buccal mucosa were performed. The histopathological examination of the lip examination showed hyperplastic stratified squamous epithelium covered with thick layer of parakeratin. Surface showed characteristic parakeratin plugging. Invasive front was regular and typically invading in pseudo-carcinomatous formation [Figure 2]. Underlying connective tissue was normal with sebaceous glands and salivary glands, which were not infiltrated. The pushing front of the lesion showed epithelial islands with the connective tissue responding by an inflammatory infiltrate. Dysplasia was absent. Margins of the lesion showed a classical change of normal epithelial stratified epithelium to the abrupt change of the lesional tissue without any evidence of malignancy suggesting features of KA [Figure 3].

Figure 2

Section showing epithelial islands invading in pseudo carcinomatous fashion. Parakeratin plugging is clearly evident. [H and E, 4× magnification]

Figure 3

Section showing abrupt change from normal stratified epithelium to the lesional tissue of keratoacanthoma. [H and E, 4× magnification]

Lesion from the buccal mucosa on histopathological examination showed hyperplasic stratified squamous epithelium exhibiting hyperorthokeratosis. The underlying connective tissue showed melanosomes and melanophages in abundance intermingling with the chronic inflammatory cell infiltrate suggestive of Leukoplakia without dysplasia and associated with focal melanosis. Secondary healing occurred uneventfully at both biopsy sites over a period of 4 weeks. After a 3-month follow-up, there was no evidence of reoccurrence of the lesion.

Discussion

KA is a relatively common skin lesion. Although cutaneous KAs are considered to arise from hair follicles, the rare cases reported occurring on mucous membranes would suggest possible origin from surface epithelium.[37] Sir Jonathan Hutchinson in 1889 provided the first description of the KA characterizing it as the “crateriform ulcer of the face,” a form of acute epithelial cancer. Freudenthal was, however, credited with coining the name “KA,” which was employed by Rook and Whimster (1950) in their report of 29 cases. Synonyms for the KA include Kyste Sebace Atypique, Molluscum Pseudo Carcinomatosum, Verrucome Avec Adenite, self-healing primary squamous carcinoma, tumor like keratosis, multiple self-healing epithelioma of the skin, and keratocarcinoma.[9] Although most early descriptions emphasized the solitary keratacanthoma;[7] the multiple familial type of KAs were first described by Ferguson Smith in 1934 and the generalized eruptive type was described by Marian Grzybowski in 1950.[910]

Ghadially et al.[11] conducted a study on the etiology of KA and concluded that acitinic factor,[7-911-16] Chemical carcinogens like pitch tar, coal and mechanic oil,[7911] trauma[6] genetics,[1718] and virus[6171119] were a contributory factor for this lesion. KA of oral cavity and lips in the Middle East is known to occur in smokers of “shisha” and “Goza,” which contains a mixture of crude tobacco fermented with molasses and fruits.”[20] Other postulated etiologic factors include chemotherapy,[21] circulating carcinogenic factors and immunologic factors.[719]

KAs are commonly found on the skin exposed to sunlight including the vermilion border of the lower lip but have also been reported on the mucous membrane of the conjuctiva, glans penis, and oral cavity.[1358111722-25] History of occupational sun exposure and long history of heavy smoking might be contributory in the present case.

KA has been reported in patients ranging from 14 to 86 years, the average age being 56 years for both males and females. Eighty percent of the patients were over 40 years of age, and the maximum incidence was in the 50–70 year age group, with the male to female ratio of 2:1.[11] The multiple KA of Ferguson Smith has its onset in adolescence.[912] Veidenheimer and Fidler estimated that keratocanthomas were one-third as common as squamous cell carcinomas, while Linell et al. in 1956 claimed that 20% of tumors formerly diagnosed as squamous cell carcinoma turned out to be KAs.[12]

There are three clinical stages in the natural history of KA as follows.

Proliferative: A rapidly enlarging papulo nodule.

Mature: A bud or hemisphere-shaped tumor with central keratinous core.

Involutional or resolving: Akeratotic necrotic tumor, leaving a puckered hypo-pigmented scar.[792226] The histogenesis of KA was first reported by MacCormic and Schaff, who suggested that the development of this lesion was attributable to hypertrophic and inflammatory, changed in sebaceous cysts. However, now the probable derivation of the cutaneous KAs from the hair follicles and of the intraoral KAs from the sebaceous glands is well accepted.[724] Ghadiallys studies classified KA into three morphologic types: type 1, bud-shaped; type 2, or dome-shaped; type 3 or berry-shaped.[7922] The latter two are considered to be of lower follicular origin and the former is evaluated as of upper follicular origin. The lesion presented in the case report was the berry type.

Apart from the solitary and multiple forms of KA, it also has several special morphologic and syndromic forms, viz., (i) agglomerate KA, (ii) KA centrifugum also known as coral-reef KA, (iii) giant KA, (iv) subungal KA, (v) intraoral and other mucous membrane KAs which can occur on the hard palate, lips and other oral sites. Because there are no hair follicles in oral mucosa, the KA may develop from ectopic sebaceous glands, (vi) multiple KAs of Ferguson Smith types (vii) multiple persistent KAs, viii) generalized eruptive KAs of Grzybowski, (ix) KAs in Torre syndrome, (x) KA in xeroderma pigmentosum, (xi) KAs in nevus sebaceous of Jodassohn.[791027]

The most important and frequent consideration in the clinical and histopathological differential diagnosis is SCC. Fortunately the morphological features and growth pattern of a KA are sufficiently distinctive to be diagnosed in most cases, KA tends to be both exophytic and endophytic with a central keratin-filled crater, whereas cutaneous SCC is mainly endophytic with ulceration often present. The crater is surrounded by overhanging epithelial “lips” which are absent in the SCC. Intraepidermal abscess are common in KA and rarely seen in SCC. In the present case, a non-healing ulcer of more than 6 weeks duration with typical bony-shape surface characterizes along with concomitant presence of bilateral leukoplakia led to the formulation of squamous cell carcinoma in clinical diagnosis. In such a clinical situation, histopathology is mainstay in diagnosis, which will confirmatively differentiates KA from squamous cell carcinoma.

The case discussed here showed the characteristic appearance histopathologically in that the normal adjacent epithelium was elevated at the margins of the lesion, with an abrupt change from normal stratified epithelium to the lesion showing a hyperplastic-stratified squamous epithelium exhibiting parakeratin plugging. The epithelial islands were invading in pseudocarcinomatous fashion and walled-off by an inflammatory infiltrate. In addition, the base of the lesion was at the level of the sebaceous glands and not beyond it. A very important factor that has to be considered for the histopathological diagnosis to be accurate is that adequate amount of marginal tissue should always be included in the biopsy. Since an excisional biopsy was performed with sufficient adjacent normal tissue, the histopathological diagnosis was confirmed in this case.

Other clinical differential diagnosis besides SCC includes verrucous carcinoma, giant condyloma acuminatum of Buschke and Lowenstein, hypertrophic acitinic keratosis, warty dyskeratoma, giant molluscum contagiosum, verruca vulgaris, metastatic cancer and deep fungal infection such as chromoblastomycosis. Small KAs seen in multiple eruptions may resemble Dariers disease.

Although the natural course of a KA is spontaneous regression, therapeutic regression is mandatory to differentiate it from SCC. Solitary KAs respond well to surgical excision. Excisional biopsy was performed in the present case as the size of the lesion was smaller in overall dimensions. Patient is still on follow-up without any evidence of recurrence. Other therapies used are cryotherapy with liquid nitrogen, electro dissection and curettage, radiation therapy, CO2 laser surgery have been used in small KAs. Intralesional or topical treatment with 5-fluorouracil, corticosteroid, bleomycin, interferon alpha-2b, and methotrexate have also been used.[27915232628]

Summary

KA is a relatively common cutaneous lesion commonly arising from hair follicles. Moreover, its occurrence on mucous membranes would suggest possible origin from surface epithelium. This paper reports a case of KA localized on the prolabium of the lower lip. Attention is focused on the difficulty of making a correct diagnosis and on the complexity of differential diagnosis with squamous cell carcinoma as the patient also presented with bilateral leukoplakia on the buccal mucosa and with a long-standing smoking history. A complete excision was carried out, and the histopathological examination of the entire neoplastic mass ruled out the presence of squamous cell carcinoma.